Motor and sensory neuroprostheses using functional neuromuscular stimulation (“FNS”) are important interventions in improving quality of life for individuals with spinal cord injury (“SCI”) or other neuro-musculo-skeletal dysfunctions. For those with thoracic level injuries, FNS can restore standing and allow for significantly enhanced mobility. While these systems can facilitate short duration activities like transferring from one surface to another, their utility for longer duration activities such as prolonged standing has been inconsistent. Some neuroprosthesis users can stand for an hour or longer, while most are limited to five minutes or less, usually because of muscle fatigue and buckling at the knee joints. Multi-contact electrodes have the potential to increase muscle recruitment and improve the performance of FNS systems for standing after SCI and other applications (e.g., diaphragm pacing, grasp, seated trunk control, sensory assistance, or any other suitable applications). By selectively activating multiple populations of motor units within a muscle or synergistic group of muscles such as the quadriceps, these electrodes can more recruit the muscle, while also allowing for stimulation paradigms that delay the onset of fatigue.
For some individuals with low cervical or thoracic level SCI who maintain upper extremity function, FNS has been used to activate paralyzed muscles in the lower extremities to facilitate standing and transfers from one surface to another. These FNS standing systems have used surface, percutaneous, and implanted electrodes with varying degrees of success. One such system, known as Parastep (available from Sigmedics Inc. of Northfield, Ill.), uses surface stimulation to extend the knees and hips during standing, and has returned mobility to over 400 people with low thoracic level SCI. However, because the Parastep system relies on surface stimulation, its performance is hampered by a number of major limitations. First, surface electrodes must be placed on the skin before each use, leading to variability in the response to stimulation and the performance of the system from day to day. Further, surface stimulation cannot selectively activate muscles that are deep within the legs, such as the knee extensor vastus intermedius, without also activating more superficial muscles, such as the biarticular knee extensor and the hip flexor rectus femoris. This limitation reduces the choice of muscles for use in surface FNS systems, and constrains the types of movements that are possible with the Parastep.
Other FNS systems for standing that use intramuscular stimulating electrodes with percutaneous leads have been shown to repeatably provide sufficient knee and hip extension for standing, and can achieve significantly better selectivity than systems using surface electrodes. However, percutaneous electrodes have exit sites where leads pass through the skin, increasing infection risk and requiring significantly more daily care than surface electrodes. They are also prone to performance degradation over time as a result of migration of the electrode away from the desired motor point.
Fully implanted FNS systems offer advantages over both surface and percutaneous stimulation systems, in that electrodes can be placed to selectively stimulate virtually any muscle, and there are no exit sites or requirements for daily care of the system. Furthermore, there is a significant cosmetic advantage to a system that is entirely implanted under the skin, rather than on or through the skin surface. One such FNS system that has been developed uses an 8-channel implanted stimulator and muscle-based (intramuscular and epimysial) electrodes to restore standing and transfer function to individuals with low cervical and thoracic level SCI. The system, which has been implanted in 18 subjects as part of a Phase II clinical trial, stimulates bilateral knee extensors (vastus lateralis), hip extensors (gluteus maximus and semimembranosus), and trunk extensors (erector spinae) to extend the knees and hips and stabilize the trunk. With this system, some subjects have been able to stand with the aid of a walker for over 45 minutes at a time, and could release one hand from the walker to perform activities of daily living. System performance has been inconsistent across subjects, however, with most experiencing much shorter standing durations. In fact, for the 11 subjects who continued to participate in the research program for at least two years after implantation, more than half never achieved standing times greater than 5 minutes. Typically, standing times were limited by knee extensor fatigue and buckling of the knee joints, which are believed to be largely attributable to the use of muscle-based electrodes in stimulating only a portion of the available knee extensor musculature.
A major limiting factor in the maximum standing times observed with the first generation implanted standing neuroprosthesis is fatigue of the vastus lateralis muscle. In order to delay the onset of fatigue and improve the functionality of neuroprostheses for standing after SCI, it is important to understand the mechanisms of fatigue in electrically stimulated muscle, so that new techniques can be developed to maintain strong contractions for longer periods of time.
Muscle fatigue is the result of a combination of factors that can lead to a rapid decrease in the force generated in response to stimulation. These factors can affect transmission at the neuromuscular junction as well as excitation-contraction coupling within the muscle itself. At the neuromuscular junction, depletion of acetylcholine can reduce transmission of action potentials from motor neurons to the muscle fibers they innervate. Within the muscle, depletion of Ca2+ stores, decreased pH as a result of lactic acid buildup, impaired impulse propagation through T tubules, and reduced availability of ATP as a result of oxygen and glycogen depletion can all cause impairment of excitation-contraction coupling. These factors can all occur simultaneously and can be highly dependent on the type of stimulation applied to the muscle. For example, constant high frequency stimulation has been demonstrated to cause impaired propagation of action potentials in the muscle, likely as a result of decreased blood flow and subsequent oxygen and ATP depletion, whereas intermittent low frequency tetanic stimulation can cause fatigue via depletion of and decreased sensitivity to Ca2+. These mechanisms occur on a variety of time scales, with Ca2+ depletion and restoration occurring on the order of seconds or faster, while oxygen and glycogen depletion can occur more slowly and have significantly longer lasting effects. In fact, constant low frequency stimulation has been demonstrated to induce significantly longer lasting fatigue, which can have effects on muscle strength 24 hours or more after it begins, with severe decreases in excitation-contraction coupling and damage to muscle sarcomeres suggested as potential mechanisms for this long-duration fatigue.